Enhanced absorption and tissue distribution of paclitaxel following oral administration of DHP 107, a novel mucoadhesive lipid dosage form.
OBJECTIVE
This study was conducted to examine the absorption and tissue distribution characteristics of paclitaxel-loaded DHP 107, a Cremophor EL-free, mucoadhesive lipid oral dosage form.


METHODS
DHP 107 was orally administered to mice at 10, 20 and 40 mg/kg doses. For comparison purposes, Taxol was i.v. injected at 5, 10 and 20 mg/kg doses. Drug levels were determined in plasma and tissues by validated HPLC assays. The absolute bioavailability and the relative distribution to various tissues were calculated as a function of dose.


RESULTS
The dose-normalized plasma AUC(DHP 107)/AUC(Taxol) ratios calculated at comparable AUC values ranged from 14.6 to 29.0%. In contrast, relative tissue distribution ratios calculated as the dose-normalized AUC(DHP 107)/AUC(Taxol) were as high as 342.0, 139.0, 112.9 and 108.2% for stomach, small intestine, large intestine and ovary, respectively.


CONCLUSIONS
Oral administration of DHP 107 provided a substantial systemic absorption of paclitaxel. Furthermore, the relative distribution ratios of DHP 107 at doses of 20 and 40 mg/kg were higher for stomach, small intestine, large intestine, and ovary than the systemic bioavailability, providing a basis for therapeutic advantages.
Shin
Beom Soo
BS
College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk, South Korea.
Kim
Hyoung Jun
HJ
Hong
Seok Hyun
SH
Lee
Jong Bong
JB
Hwang
Sang Wook
SW
Lee
Mann Hyung
MH
Yoo
Sun Dong
SD
D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005079:Excipients / Q000737:chemistry*; D005260:Female; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D005079:Excipients; D008055:Lipids; D017239:Paclitaxel